This is a shared instrumentation proposal to acquire an ACUSON SequoiaTM C512 cardiac ultrasound imaging system, manufactured by Siemens Medical Solutions USA, Inc. Echocardiography is widely accepted as a valuable research tool for studying a broad range of cardiovascular disease processes in small animals, including ischemic heart disease, heart failure, cardiac hypertrophy and remodeling, hypertension and diabetic cardiomyopathy. Although the University of Toledo has nationally recognized NIH-funded investigators working in many of these areas, the university currently does not have adequate access to an ultrasound machine that is capable of providing in-depth cardiac assessment of small research animals. Consequently, investigators have had to seek alternative, invasive approaches to assessing cardiac function and remodeling, leading to higher costs, increased animal use and lower efficiency. By meeting a critical need for small animal echocardiography, the acquisition of the ACUSON Sequoia system will greatly facilitate progress on active NIH-sponsored R01 projects as well as a Program Project Grant (2P01) directed by the major users. In addition, access to this shared equipment will be extended to minor users and new users who have active grant support or are seeking to develop preliminary data for new grant applications. The equipment will be located in the Cardiovascular Phenotyping Core Laboratory of the Department of Physiology and Pharmacology on the University of Toledo's Health Science Campus, and space within the lab will be allocated to facilitate studies for all users. The day-to-day scheduling, training, and technical support for the instrument will be handled under the auspices of the Core Laboratory, with administrative supervision from the PI and an Internal Advisory Committee. Institutional support for the instrument will come in the form of space allocation and a 50% subsidy for the annual service contract. Ongoing projects that will benefit from the Sequoia system include: 1) Studies aimed at exploring mechanisms of digitalis mediated cardiac myocyte hypertrophy;2) Studies of the molecular interactions that constitute the formation of the Na/K-ATPase/Src receptor complex, and to evaluate the functionality and physiologic response of this newly discovered receptor in digitalis- activated signal transduction in the heart;3) Studies to identify genetic determinants of blood pressure and their effects on cardiac function and remodeling;and 4) Studies aimed at identifying the mechanisms by which insulin resistance leads to metabolic syndrome and its associated cardiovascular effects. Several new projects focused on cardiac fatty acid metabolism, uremic cardiomyopathy, the role of calpains in the repair of the damaged plasma membranes of damaged cardiomyoctes, and the role of TRPC3 channels in atherogenesis and the development of left ventricular hypertrophy will also benefit from the availability of the requested imaging system. By accelerating progress on these diverse projects, this shared instrumentation will have a major positive impact on health-related research at the University of Toledo. PUBLIC HEALTH RELEVANCE: We are requesting funds to acquire an ACUSON SequoiaTM C512 cardiac ultrasound system, which is a well established instrument with an excellent performance record and widespread acceptance of echocardiographic data generated from large and small research animals alike. This instrument is not currently available at this university. It will be operated as a shared resource to accelerate the cardiovascular-related research of numerous investigators including three major users who are engaged in NIH-sponsored projects focused on cardiac hypertrophy, hypertension and diabetes.